Australasian Insights and Perspectives on the Burden of Chronic Liver Disease
Authors: Annie Zhou, Rohit Sawhney
Journal: Clinical Gastroenterology and Hepatology (2023)

We read with great interest the recent important update by Younossi et al1Younossi Z.M. et al.Clin Gastroenterol Hepatol. 2023; 21: 1978-1991Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar detailing the global burden of chronic liver disease (CLD), highlighting changing patterns and regional variations. The authors note increasing rates of hepatocellular carcinoma (HCC) in high sociodemographic index regions including Australasia but specific data on prevalence of different etiologies of CLD and associated disease burden in this region have not been well described in this or other global reports.2Asrani S.K. et al.J Hepatol. 2019; 70: 151-171Abstract Full Text Full Text PDF PubMed Scopus (1954) Google Scholar We wish to share additional perspectives from the Australasia region that may provide further insights into epidemiologic and sociodemographic factors impacting the burden of CLD. Australia and New Zealand display population characteristics that distinguish them from adjoining regions and other high sociodemographic index countries. Australia has a significant migrant population with one-quarter of people being born overseas; New Zealand has a similar proportion of people identifying as Māori or Pacific Island origin. This is reflected in the prevalent causes of cirrhosis, with Global Burden of Disease 2017 data indicating the proportion of cases caused by hepatitis B virus in Australasia is much higher than North America and similar to high-income Asia-Pacific nations, whereas the burden of nonalcoholic fatty liver disease (NAFLD) is more synonymous with North America than Asia-Pacific.3Global Burden of Disease 2017 Cirrhosis CollaboratorsLancet Gastroenterol Hepatol. 2020; 5: 245-266Abstract Full Text Full Text PDF PubMed Scopus (782) Google Scholar Prospectively collected Australia and New Zealand Liver Transplant Registry (ANZLTR) data provide information regarding long-term trends in etiologies of CLD. The proportion of patients undergoing liver transplantation (LT) for alcohol-related liver disease has remained constant but recently surpassed hepatitis C virus as the leading indication for LT, following significant decline in hepatitis C virus–related LT since the advent of direct-acting antivirals.4Howell J. et al.Transplant Direct. 2022; 8: e1345Crossref PubMed Scopus (1) Google Scholar Similarly, LT cases for hepatitis B virus have decreased significantly over time, because of availability of antiviral therapy and universal neonatal vaccination. However, the proportion of LTs for NAFLD has increased significantly, and is now the third most common etiology for CLD requiring LT.4Howell J. et al.Transplant Direct. 2022; 8: e1345Crossref PubMed Scopus (1) Google Scholar Similar trends were seen for patients undergoing LT for HCC with a significant increase in the percentage with underlying NAFLD. This correlates with the epidemic of obesity and metabolic syndrome in Australasia and is consistent with the increased rates of HCC in the region described by Younossi et al.1Younossi Z.M. et al.Clin Gastroenterol Hepatol. 2023; 21: 1978-1991Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar The diverse population and disease burden in Australasia also present a valuable opportunity to evaluate the prevalence and impact of concurrent liver diseases on clinical outcomes. ANZLTR data have demonstrated the proportion of LT recipients with >1 CLD or cofactor has increased significantly over time, related to increases in alcohol-related liver disease and NAFLD, and was significantly associated with HCC but with no difference in posttransplant survival.4Howell J. et al.Transplant Direct. 2022; 8: e1345Crossref PubMed Scopus (1) Google Scholar However, a large population-level study in 1 Australian state using data linkage in patients hospitalized with hepatitis C virus indicated significant associations between alcohol use disorder and decompensation, HCC, and liver-related mortality despite overall decrease in morbidity and mortality with direct-acting antivirals therapy, emphasizing the importance of addressing cofactors and comorbidities.5Alavi M. et al.J Hepatol. 2019; 71: 281-288Abstract Full Text Full Text PDF PubMed Scopus (68) Google Scholar We also note significant variability in the prevalence rates of CLD reported by global organizations including the World Health Organization, Global Burden of Disease, and Polaris Observatory. Substantial findings are based on modelling, relying on robust national and regional data which is often lacking, or on cohort studies rather than true population-level data. This certainly applies in Australasia with studies capturing data in localized regions, using cancer or transplant registries and data linkage but with no national cirrhosis registry to more accurately estimate CLD prevalence. The aforementioned study on concurrent liver diseases in patients with LT highlights potentially significant underreporting of the true burden of CLD requiring LT given many international LT registries report the primary diagnosis only. There is also significant variation between areas within our region and among high-risk population groups, likely influenced by remoteness, comorbid, and sociodemographic factors. We call particular attention to significant disparities in disease burden and outcomes between indigenous and nonindigenous people. Studies have demonstrated a disproportionately high prevalence of viral hepatitis and HCC in indigenous Australian and Māori people, and significantly higher mortality rates.6Clough S. et al.N Z Med J. 2022; 135: 91-104PubMed Google Scholar,7Wigg A.J. et al.EClinicalMedicine. 2021; 36100919Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar A retrospective population-based cohort study of patients hospitalized for cirrhosis in 1 Australian state reported higher readmission rates, greater proportion of alcohol-related liver disease, and lower survival among indigenous patients compared with other Australians.8Valery P.C. et al.Int J Equity Health. 2020; 19: 27Crossref PubMed Scopus (11) Google Scholar Another large cohort study across 3 states examined epidemiologic factors in HCC and confirmed poorer survival in indigenous Australians but demonstrated this was mainly driven by higher rurality, comorbidities, and HCC cofactors along with lower socioeconomic status and receipt of curative therapy rather than according to indigenous status, highlighting the crucial importance of sociodemographic factors and barriers to care.7Wigg A.J. et al.EClinicalMedicine. 2021; 36100919Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar We therefore reiterate the valuable global perspectives provided by Younossi et al1Younossi Z.M. et al.Clin Gastroenterol Hepatol. 2023; 21: 1978-1991Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar on the burden of CLD and HCC, recognizing regional and sociodemographic influences. Experience from Australasia supports the need for further comprehensive data across regions, particularly in populations with sociodemographic disparities and concurrent disease, to better inform health policy and target interventions. The Global Burden of Liver DiseaseClinical Gastroenterology and HepatologyVol. 21Issue 8PreviewChronic liver disease (CLD) and its associated complications (cirrhosis and liver cancer) cause significant mortality, morbidity, and economic burden. Published data from the World Health Organization and/or the Global Burden of Disease show that the burden of CLD is large and increasing, primarily owing to the increasing burden of nonalcoholic fatty liver disease and alcohol-related liver disease (ALD). Middle Eastern, Northern African, and Asian regions of the globe are most affected by hepatitis B and hepatitis C virus. Full-Text PDF Open AccessReplyClinical Gastroenterology and HepatologyVol. 22Issue 4PreviewWe thank Zhou et al1 for their careful and thoughtful review of our manuscript reporting the global burden of chronic liver disease (CLD).1 Zhou et al1 noted the shortcomings of the Global Burden of Disease (GBD) dataset to provide accurate regional data about the etiologies of CLD-related hepatocellular carcinoma.2 In this context, they shared their insights on particular CLD etiologies for hepatocellular carcinoma with the data gathered from national databases for the Australasia region.1 Full-Text PDF